Ibogaine: A Comprehensive Analysis of its Development by ATAI Life Sciences and DemeRx for Substance Use Disorders

I. Executive Summary

Ibogaine, a psychoactive indole alkaloid derived from the Tabernanthe iboga plant, has a long history of traditional use in West African spiritual practices and has garnered significant interest for its potential in treating substance use disorders (SUDs). This report provides a comprehensive analysis of ibogaine and its metabolite noribogaine, focusing on the development programs led by DemeRx, Inc. and its collaboration with, and subsequent program acquisition by, ATAI Life Sciences.

The primary therapeutic focus for ibogaine (as DMX-1002) has been Opioid Use Disorder (OUD), driven by anecdotal evidence of its ability to interrupt addiction and alleviate withdrawal. Noribogaine (as DMX-1001), an active metabolite, is being developed by DemeRx for Alcohol Use Disorder (AUD), with a rationale centered on retaining therapeutic benefits while potentially mitigating ibogaine's psychedelic effects and safety concerns.

The DMX-1002 program, under ATAI Life Sciences, completed a Phase 1 trial (NCT05029401) which, while meeting pharmacokinetic endpoints, highlighted QTc prolongation as a significant safety signal. Despite initial plans to advance to Phase 2a, DMX-1002 has been conspicuously absent from ATAI's recent pipeline updates, suggesting a strategic deprioritization or discontinuation, likely influenced by the safety profile and regulatory complexities associated with a Schedule I substance.